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USMLE - Pharm

Kaplan Section 7 - Anticoagulants

What happens to fibrinogen in the coagulation process? soluble fibrinogen is transformed into insoluble fibrinogen
What are anticoagulants? Drugs that decrease the formation of fibrin clots
What does warfarin do? Oral anti-coagulant. Inhibit the hepatic SYNTHESIS of clotting factors 2, 7, 9, and 10
What is warfarin? derivative of vitamin K
What does heparin do? IV anti-coagulant. Activation of anti-thrombin III --> Inhibit the ACTIVITY of ACTIVATED clotting factors (esp 2a and 10a)
Which are the endogenous anticoagulants? Protein C and S
What do the endogenous anti-coagulants do? cause proteolysis of factors 5a and 8a
Heparin and Warfarin: which is a large polysaccharide, and which is a small molecule? large polysaccharide = heparin; small molecule = warfarin
Heparin and Warfarin: which is lipid soluble, and which is water soluble? water soluble = heparin; lipid soluble = warfarin
Heparin and Warfarin: which is a vitamin K derivative? Warfarin
Heparin and Warfarin: which is given orally and which is given parenterally? Hep = IV/subQ, Warfarin = PO
Heparin and Warfarin: which is metabolized in the liver? Warfarin
Heparin and Warfarin: which has hepatic and reticuloendothelial elimination? Heparin
Heparin and Warfarin: which is 98% protein bound? Warfarin
Heparin and Warfarin: which has a longer half life? What are the half lives? Warfarin = 30+ hours (this is why you can take it orally at home); Heparin = 2 hr (this is why it's IV in the hosp)
Heparin and Warfarin: which can cross the placenta? Heparin can't. Warfarin can and is teratogenic! Pregnant people can't be on warfarin!
What is the mechanism of heparin? Binds to antithrombin III --> increases its inhibition of factors 12a, 11a, 9a, 10a, and 2a.
What is the mechanism of warfarin? Prevent gamma-carboxylation --> decrease hepatic synthesis of the vitaminK-dependent factors (2,7,9,10)
What are the vitaminK-dependent factors in the coagulation cascade? 2,7,9,10, protein C & S
What should you note about the onset of warfarin? it has no effect on the vitaminK-dependent factors already present - it only inhibits synthesis of new factors that are vitK-dependent, so onset takes longer because the ones present have to die off!
How to monitor warfarin? PT/INR
How to monitor heparin? PTT
How to antagnize warfarin? Use protamine sulfate - fast onset
How to antagnize warfarin? Slow - give Vitamin K; fast - give fresh frozen plasma that should already have a supply of the vitaminK-dependent factors used in the coag cascade
Heparin and Warfarin: which to use for rapid anticoagulation for thromboses? Heparin
Heparin and Warfarin: which to use for longer-term anticoagulation for thromboses? Warfarin
Heparin and Warfarin: which to use for unstable angina? Heparin
Heparin and Warfarin: which to use for DIC? Heparin
Heparin and Warfarin: which to use for post-MI? Warfarin
Heparin and Warfarin: which to use for atrial arrhythmias? Warfarin
Heparin and Warfarin: which to use for heart valve damage? Warfarin
Heparin and Warfarin: which to use for open heart surgery? Heparin
What is a dangerous adverse effect of heparin? Heparin-induced thrombocytopenia (HIT) - low platelet count due to the administration of heparin; thrombosis is a complication (clots).
Heparin and Warfarin: which can cause osteoporosis? Heparin
Heparin and Warfarin: which can cause skin necrosis if low protein C? Warfarin
Heparin and Warfarin: which causes more drug interactions? Warfarin (metabolized by CYP450)
Heparin and Warfarin: which is more likely to cause hypersensitivity? Heparin
What is the advantage of low MW heparin vs. regular heparin? 1. longer 1/2 life, 2. less thrombocytopenia, 3. enhanced activity against factor 10a
What is danaparoid? heparin of a different structure -- safer in pts who have hypersensitivity rxn to heparin
How do bile acid sequestrants affect the oral absorption of warfarin? decreases oral absorption of heparin
Is warfarin an acidic or basic molecule? acidic
If warfarin is used in conjunction with other drugs that also bind plasma proteins, what will happen? It binds plasma proteins weakly, but extensively. If other drugs displace warfarin's binding to plasma proteins --> inc free fraction of warfarin --> increase anti-coag effect!
What happens to warfarin if used in conjunction with ASA/cimetidine/metronidazole/phenytoin/sulfonamides? warfarin's actions increased
What happens to warfarin if used in conjunction with barbiturates/carbamazepine/cholestyramine/rifampin/thiazides/vitamin K? warfarin's actions decreased!
What is the role of protein C and protein S? Endogenous anti-cogulants; they block the cofactors 5 and 8
What happens when a person does not have protein C? hypercoagulation state
Put these coagulation factors in increasing order of half life duration: 2a, 7a, 9a, 10a, protein C 7 sees "C's" 9 and 10, too "2"!: 7a (8hr = 1/3 day) < protein C (14 hr = 1/2 day) < 9a (24 hr = 1 day) < 10a (40 hr ~ 2 days) < 2a (60 hr ~ 3 days)
When treating with warfarin, what factors are depleted first? 7 and protein C because they have the shortest half lives. Therefore, with warfarin, the extrinsic pathway is inactivated, while the intrinsic remains active for a few days longer.
What is the consequence of initial warfarin treatment? Since protein C is depleted --> hypercoagulability --> dermal vascular thrombosis and skin necrosis
What are fibrinolytics? drugs that lyse thrombi by catalyzing plasminogen --> plasmin
Name some fibrinolytics tissue plasminogen activator (tPA), streptokinase (antibacterial)
When would you use thrombolytics? 1. coronary thromboses in MI, 2. deep venous thromboses, 3. pulmonary embolism, and 4. ischemic stroke (tPA)
What thrombolytic would you use for ischemic stroke? tPA
What does plasmin do? degrades blood clots
What activates the conversion of plasminogen to plasmin? fibrin (factor 1a) as well as tPA
How does streptokinase work? Binds to both bound and free plasminogen (not clot specific) --> depletes circulating fibrinogen, factor 5 and factor 8
Why wouldn't you want to use streptokinase as a thrombolytic in someone who's previously had a B-hemolytic streptococci infection? Streptokinase will bind to antigens that it recognizes, so those with the antigens --> decreased streptokinase activity for thrombolytics
What is alteplase? tPA - clot-specific drug. Acts on plasminogen that is bound to fibrin (fibrin is activating the plasminogen). No allergy problems)
What is the most important factor in maximizing the effectiveness of thrombolytics? Early administration!! (> 60% decrease in mortality post-MI if used within 3 hrs)
Thrombolytics + ASA post MI further decrease in mortality
Thrombolytics + adenosine post MI decreases size of infarction
Which thrombolytic can cause hypersensitivity rxns? streptokinase
Which thrombolytic can cause hypotn? streptokinase
What are antidotes to thrombolytics? If excessive bleeding, can use aminocaproic and tranexamic acids - both are antifibrinolysins
What is the difference between thrombolytics and antiplatelet drugs? One breaks up the clot, while the other keeps the clot from forming in the first place
Name compounds that increase platelet aggregation. 5 ATTa: 5HT, thrombin, TXA2, a2 agonists
Name compounds that decrease platelet aggregation. cAMP PAD goes TIC toc clip CLOP: cAMP, PGI2, ASA, dipyridamole, ticlopidine, clpidogrel
Name some anti-platelet drugs 1. ASA, 2. ticlopidine, 3. clopidogrel, 4. abciximab, 5. eptifibatide, 6. tirofiban
What is the mechanism of ASA's antiplatelet action? Irreversibly inhibits COX in platelets --> decrease platelet aggregation
What does low dose ASA do? prevent MI and recurrence
For what is ASA used prophylactically atrial arrhythmias and TIA's
What are toclopidine and clopidogrel? Antiplatelet drugs.
What is the mechanism of toclopidine and clopidogrel? blocks ADP receptors on platelets --> decrease activation
When should you use toclopidine and clopidogrel? as ASA alternatives for: 1. TIA's, 2. post-MI, 3. unstable angina
What are some adverse effects of toclopidine and clopidogrel? 1. hemorrhage, 2. leukopenia, 3. thrombocutopenic purpura
What are abciximab, epitifibatide, and tirofiban? Antiplatelet drugs.
What is the mechanism of abciximab, epitifibatide, and tirofiban? antagonists that bind to glycoprotein 2b/3a receptors --> decrease aggregation by preventing the cross-linking rxn
When to use abciximab, epitifibatide, and tirofiban? 1. acute coronary syndromes, 2. post-angioplasty
What is enoxaparin? LMW heparin derivative
Created by: christinapham